Polypharmacy prescribing guidance - draft: consultation

4. General Principles

4.1 What is polypharmacy and why is it important?

Medication is by far the most common form of medical intervention for many acute and chronic conditions. Medication can be highly effective in preventing or slowing disease progression, with guidelines for single conditions recommending the use of a variety of evidence-based medicines. However, there is often a mismatch between prescribing guidelines for specific medical conditions and the range of clinical complexity found in individuals. For those with complex multiple conditions, frailty, a dominant condition (e.g. dementia) or approaching the end of their lives, the implementation of the sum of evidence-based recommendations may not be rational, may increase the risk of medicine related harm and may not align with the individual’s preferences.

The term polypharmacy itself just means “many medications” and is defined to be present when a person takes two or more medicines. When polypharmacy is beneficial, it is considered ‘appropriate’. For example, treatment of left ventricular systolic dysfunction (heart failure) may include the use of several different classes of drugs.

Appropriate polypharmacy is present, when:

a. all medicines are prescribed for the purpose of achieving specific therapeutic objectives that have been agreed with the individual

b. therapeutic objectives are actually being achieved or there is a reasonable chance they will be achieved in the future

c. medication has been optimised to minimise the risk of adverse drug reactions (ADRs) and,

d. the individual is motivated and able to take all medicines as intended.

Inappropriate polypharmacy is present, when one or more medicines are prescribed that are not or no longer needed, either because:

a. there is no evidence-based indication, the indication has expired, or the dose is unnecessarily high

b. one or more medicines fail to achieve the therapeutic objectives they are intended to achieve

c. one, or the combination of several medicines cause unacceptable ADRs, or put the individual at an unacceptably high risk of such ADRs, or

d. they are not willing or able to take one or more medicines as intended.

The appropriateness of polypharmacy should be considered at each initiation of new treatments for the individual, and when the person moves across different health care settings, that is, through transitions of care. The increased risk of harm is not always offset by increased benefits, and for many preventive medicines, such benefits may never be realised due to a limited life expectancy. The risk of harm is generally higher in older people with multimorbidity than in younger people due to pharmacokinetic factors, such as reduced ability to clear medication (e.g. kidney and/or liver impairment); pharmacodynamic factors such as increased vulnerability to medication related harm (e.g. general frailty, drug–drug and drug–disease interactions); and medication burden.[14]^,[15],[16]

There are five clear stages when appropriate polypharmacy requires consideration:

1. Prescribing (and risk assessment)

2. Medication review

3. Dispensing and administration

4. Communication and patient engagement

5. Medication reconciliation (at care transitions)

The majority of harm, 53% occurs at the ordering/ prescribing stage and 36% at the monitoring/ reporting stage, with 80% of the avoidable harm arising ordering/ prescribing stage.8 Although Polypharmacy Guidance: Appropriate Prescribing - Making medicines safe, effective and sustainable 2025-2028 concentrates on a holistic 7-Steps person-centred medication review, the principles, tools and recommendations can be used at any time, especially at the initiation of medication and when a person moves across the care transitions.

4.2 Causes of inappropriate polypharmacy

Poor co-ordination of care increases the likelihood of polypharmacy and medication related harm. For instance, people with multimorbidity often receive care from multiple prescribers and have complex medication regimen. [17] This can result in communication breakdown between the different prescribers and healthcare professionals, and fragmentation of care.17^,[18] There may be a reluctance to alter medication initiated by another prescriber across the interfaces of care, e.g. during a hospital admission or initiated by a specialist. [19] This highlights that medication review is a dynamic process and healthcare professionals need to be empowered to re-assess the appropriateness of medication at all stages of the individual’s journey. This will need cultural change to address patient safety and improved communication across all care settings.19

Primary care prescribers can also feel that they are not empowered to alter medication commenced in another part of the health service, such as during a hospital admission or in a specialist clinic. Prescribers reviewing adults with multiple conditions need to be trained and empowered to review decisions throughout an individual’s journey taking into account factors that may not have been present, or taken account of, at the time of initial prescription. This requires improved communication between care settings and movement across care transitions can present an opportunity to identify and reduce inappropriate polypharmacy.[20]^,[21]

4.3 The prescribing cascade

A ‘prescribing cascade’ arises when an adverse drug event occurs that is misinterpreted as a new medical condition, and a subsequent medication is prescribed.^[22] This may contribute to additional adverse effects, for instance, initiating a diuretic for oedema associated with a dihydropyridine calcium channel blocker may put the person at risk of fluid depletion. Another example is the prescribing of a proton pump inhibitor (PPI) due to gastro-intestinal (GI) irritation caused by prescribing of non-steroidal anti-inflammatory drug (NSAID).

4.4 Medicines implicated in causing harm: High Risk Medicines

Medication related harm accounts for half of all preventable harm in healthcare. A recent systematic review found that the prevalence of medication related harm globally is 1 in 20, where one fourth of the harm was potentially serious or life threatening.8 The majority of harm, 53% occurs at the ordering/ prescribing stage and 36% at the monitoring/ reporting stage, where 80% of the avoidable harm arising ordering/ prescribing stage.8 At least a quarter of this preventable harm was found to range from severe to potentially life threatening. The highest prevalence rate was found in the older person with high comorbidities and polypharmacy. This was greatest in medicines affecting the central nervous system and the cardiovascular system.

High-risk medicines are those that have an increased risk of causing significant harm or death if they are misused or used in error. [23]^, [24] Errors with these medicines are not necessarily more common than with other medicines, but the consequences can be more devastating.23^,24 Medicines considered ‘high-risk’ vary between hospitals and other healthcare settings, such as primary and care of the elderly, and depend on the context and the clinical conditions treated.23^,24

The acronym ‘A-PINCHS’ is used for example in hospital settings, to highlight specific medicines in the categories known to cause harm in the organisation or setting.24

List 1: Most common classes of medicines causing harm in the hospital setting

A Anti-infectives

P Potassium and other electrolytes

I Insulin and other hypoglycaemic agents

N Narcotics and other sedatives

C Chemotherapeutic agents

H Heparin and anticoagulants

S Systems

Many of the medicines above will be recognised as high risk regardless of the setting such as opioids and insulin. However, many medicines in common usage, when taken together with other medicines, or due to a change of physiology for the individual e.g. impaired kidney function, are responsible for the potential adverse effects. In these scenarios the potential benefits should be considered against the potential adverse effects.

Table 1: Common medications that have the potential to cause harm and factors to consider

Medication group /medication	Examples of individual medications	Issues/ important areas to consider [25],[26]
Angiotensin converting enzyme inhibitors (ACE inhibitors)/ Angiotensin II receptor antagonists (ARB)	Ramipril, enalapril, captopril, lisinopril, perindopril, irbesartan, losartan	The indication for ACE inhibitors and A2RA and the evidence base for their use, symptomatic such as in heart failure or secondary prevention Kidney function before starting and while titrating the dosage Can also cause a drop in BP and cause dizziness and falls
Antibiotics	Cephalosporins (e.g. cefalexin), penicillins (e.g. amoxicillin), quinolones (e.g. ciprofloxacin), macrolides (e.g. azithromycin)	Use antibiotics only when indicated and avoid prophylactic use in care homes Commonly used antibiotics, such as cephalosporins, fluoroquinolones and amoxycillin with clavulanic acid increase the risk of C. difficile and antimicrobial resistance
Antidepressants	Fluoxetine, paroxetine, amitriptyline, citalopram, venlafaxine, dosulepin	Antidepressants have been implicated in causing falls Tricyclic antidepressants have more anticholinergic and cardiotoxic effects than other antidepressants and should be used with caution in those with cardiovascular or cognitive comorbidities
Antithrombotics	Antiplatelet agents (e.g. aspirin, clopidogrel) Oral anticoagulants (warfarin and direct oral anticoagulants [DOACs] e.g. dabigatran, edoxaban rivaroxaban, apixaban)	Consider kidney function. Kidney function declines as people age, which has an impact on the dose and suitability of DOACs Individual factors can contribute to increased risk of bleeding, such as age, previous bleeding or stroke, raised blood pressure, reduced kidney/liver function and drug-drug interactions. Review dual antiplatelet therapy and its intended duration, due to the risk of gastro-intestinal haemorrhage
Beta-blockers	Atenolol, propranolol, sotalol, bisoprolol, metoprolol, carvedilol	Adverse effects such as bradycardia and fatigue can be exacerbated with age, frailty and by drug-drug interactions
Chemotherapy	There are various agents that fall into this category	Neutropenic sepsis, sepsis, constipation, deranged electrolytes, rash, thrombocytopenia
Digoxin	-	Kidney function, electrolytes and digoxin serum concentration require monitoring Drug-drug interactions can impact on digoxin clearance and increase toxicity
Diuretics	Furosemide, bendroflumethiazide, bumetanide, spironolactone	Potent diuretics, useful for symptomatic management (e.g. of heart failure), require regular review due to risk of hypotension and electrolyte disturbances
Hypoglycaemic agents	Insulin, sulfonylureas (e.g. glibenclamide, glipizide)	Intensive glycaemic control strategies markedly increase the risk of hypoglycaemia, associated with increased mortality, cardiovascular events, falls, and accidents,[27] especially sulfonylureas in over 75-year-old persons
Leukotriene receptor antagonist	Montelukast	Risk of neuropsychiatric reactions, including new or worsening changes in mood, sleep, or behaviour. Discontinue use if individuals develop new or worsening neuropsychiatric symptoms[28]
Mood stabilisers	Lithium	Lithium concentrations require regular monitoring, especially when other medicines are added or withdrawn, or with changes to the patient’s clinical conditions (e.g. kidney impairment, dehydration) Adverse effects that can develop over time and require dosage adjustment
Non-steroidal anti-inflammatory drugs (NSAIDs)	Diclofenac, ibuprofen, celecoxib, ketoprofen, naproxen	NSAIDs and antiplatelet agents was the leading cause of drug-related hospital admissions, accounting for approximately a third of all drug-related admissions and half of drug-related deaths. [29] This is exacerbated with a history of peptic ulcer disease and the use of several medicines, including antiplatelets, anticoagulants, corticosteroids, and selective serotonin reuptake inhibitors In those at highest risk of GI bleeding, if treatment with NSAID is unavoidable, consider gastroprotection (usually with a proton pump inhibitor) Cardiovascular risk associated with many of the NSAIDs
Opioids	Morphine, dihydrocodeine, codeine (± paracetamol) tramadol, fentanyl	There is little evidence for the long-term use of opioids in long-term, non-malignant pain. Adverse effects such as respiratory and cognitive dysfunction is exacerbated with drug-drug interactions and altered pharmacodynamics in older person
Psychotropic agents	Benzodiazepines and z-drugs (e.g. diazepam, nitrazepam, temazepam, zopiclone)	Long-term use of hypnotics and anxiolytics in general practice is not appropriate, maximum duration for most people is three to four weeks [30] Long-term use is associated with numerous risks, including drowsiness and falls, forgetfulness, confusion, depression, irritability, aggression, impulsivity, digestive problems, and dependence
Antipsychotics (e.g. olanzapine, clozapine, quetiapine)	Antipsychotics are frequently prescribed to reduce symptoms of stress and distress in people with dementia. However, these drugs have (time) limited benefits, and older patients are particularly vulnerable to their adverse effects.[31] They should therefore be used as the last resource Long-term use is associated with cerebrovascular events and death in people with dementia [32]
Proton Pump Inhibitors	Lansoprazole, omeprazole, esomeprazole, pantoprazole	Hypomagnesaemia, hyponatraemia, Clostridium difficile
Steroid Inhaler	Various ICS	Pneumonia, oral thrush
Systemic corticosteroids	Prednisolone	Require ongoing review to wean or use the lowest, effective dose Adverse effects with long-term use necessitate management, such as osteoporosis and glaucoma Consider adrenal suppression with prolonged use, increases susceptibility to infections

*adapted from Komagamine,^[33] Agrawal,[34] Pirmohamed29 and Osanlou10

(Reproduced with permission from Polypharmacy and Deprescribing: Pharmacovigilance and Drug Safety in Clinical Practice)

4.5 Interventions for those with polypharmacy

A systematic review concluded that preventable medication related harm remains a frequent and enduring serious problem, causing severe or potentially life-threatening outcomes in over a quarter of all preventable harm cases. [35] The risk is particularly high in inpatient care settings, geriatric care, specialised care settings, intensive care and emergency departments. ^[36] A person-centred approach to address their needs enables self-management. Involving individuals in decisions has been shown to address up to 15% of harm. ^[37] Public involvement is also important in changing policy[38] as well as nudge theory to support behaviour change, human factors, and change management for a scalable, sustainable solution to preventable medication-related harm due to inappropriate polypharmacy.

A rapid review of nine systematic reviews including international studies on polypharmacy ^[39] assessed the burden of problematic polypharmacy. While all systematic reviews showed an improvement in reducing inappropriate polypharmacy, the impact on other outcomes was mixed and the quality of the evidence was variable. From a safety perspective, Page et al. found no evidence to suggest that deprescribing increases the risk of adverse outcomes,[40] suggesting deprescribing following a medication review is a possible way to reduce inappropriate polypharmacy. This adds an important contribution as one of the challenges when addressing inappropriate polypharmacy is confidence by prescribers to reduce or stop medication originally intended for long-term use, for fear of harm to the individual.

NHS Scotland introduced a person-centred programme for medication review to address inappropriate polypharmacy. This drew on work from indicators developed by Pirmohamed et al. (which identified a list of high-risk medications),²⁹ the pharmacist-led information technology intervention for medication errors (PINCER trial), ^[41] and the Data-Driven Quality Improvement in Primary Care (DQIP) programme. ^[42]

The DQIP programme evaluated indicator-based case finding and decision support, combined with education and financial incentives for medication review. This was a cluster randomised controlled trial and included 34 general practices in Scotland. The DQIP intervention significantly reduced high-risk prescribing (of NSAIDs and antiplatelets) by 37% and reduced associated emergency hospital admissions (for gastro-intestinal bleeding by 34%, for heart failure by 27%, and for acute kidney injury by 14%). The PINCER trial showed that a pharmacist-delivered information technology intervention substantially reduced the frequency of a range of clinically important prescription and medication monitoring errors. Related qualitative work showed the acceptability of the PINCER intervention to general practices, and staff valued the additional educational input and support provided by the pharmacist.

Translation of learning from these safety prescribing programmes in Scotland was achieved by inclusion into national polypharmacy guidance,²⁵ by adopting the key recommendations from SIMPATHY and using the 7-Steps medication review process. This is supported by a suite of 69 indicators to identify individuals most at risk and 27 polypharmacy outcome indicators at a national level to show the improvements in reduction of medication related harm. ^[43]

A rapid review of polypharmacy guidelines and studies was undertaken in November 2023. These were reviewed to consider any additional evidence and insights, and support the person-centred approach to address inappropriate polypharmacy, appreciating that there may need to be additional therapy to achieve therapeutic objectives, for example to improve symptomatic control for heart failure. This ensures that the focus is on improving patient outcomes with medicines. The outcomes since then of the iSIMPATHY project have provided the validated methodology to achieve this.9 Studies are needed to explore the potential of pharmacogenomic interventions to improve the outcomes of people with multimorbidity where multiple medications are indicated. This could be undertaken in the context of a medication review.

There is the need to address barriers and support facilitators to deal with the change management methodologies outlined in both SIMPATHY2 and iSIMPATHY.9 Key tools such as PESTEL and SWOT can be used to highlight these, as well as Kotter to ensure implementation.9^,[44],[45]

4.6 7-Steps Medication Review Process

The person-centred 7-Steps review process starts by matching therapeutic objectives to current life priorities with the individual. This is illustrated in Figure 2 below. This initial discussion guides decision-making in subsequent steps that consider medication need, effectiveness, and safety before a therapeutic plan and follow-up strategy are agreed upon. Applying the 7-Steps as part of a holistic medication review has the potential to address all six dimensions of quality in health care: efficacy, safety, efficiency, timeliness, equity, and acceptability.25 Although the 7-Steps approach was primarily designed to be applied at the point of medication review to correct inappropriate prescribing, its principles may equally be applied when initiating new medicines, to prevent inappropriate prescribing, or when a patient moves across transitions of care. This may result in reducing the dose or stopping a medication completely, although this should not be the primary objective of a medication review. Addressing unmet needs may include starting new medications.

The actions undertaken in each step are summarised, and begin with asking “what matters to the patient?”

• Step 1: sets the context within which all further decisions are made, namely establishing what matters to the patient
• Step 2: identify essential treatment
• Step 3: determine if the patient is taking unnecessary treatment
• Step 4: identify whether therapeutic objectives that matter to the patient are achieved and that there is evidence of the effectiveness of the medicines (NNT)
• Step 5: assess if any medicines are too risky or cause unacceptable adverse effects
• Step 6: consider which medicines are cost-effective and environmentally sustainable
• Step 7: determine whether the patient is willing and able to manage their medicines in a way that avoids harm and maximises benefit.

In order to support the reviews, Appendix B highlights common medicines that may be relevant to review at each of the 7-Steps.

More detail in application of the 7-Steps can be found in the case study examples in Section 9.

4.7 Efficacy of Medicines: Numbers Needed to Treat (NNT)

What is an NNT?

The Scottish Government Polypharmacy Guidance intends to be a practical tool to help prescribers decide when it is appropriate to initiate and continue long-term medicines. In some circumstances it may be appropriate to discontinue treatments. Presentation of the number needed to treat (NNT) for a range of medicines is a tool that prescribers may use to aid discussions with individuals.

Originally described by Laupacis et al.^[46] and cited in Cook and Sackett,^[47] the NNT was introduced as an approach to summarise the effect of treatment in terms of the number of people that need to be treated with a particular therapy to expect to prevent one adverse event over a specified time period.

The NNT is defined as the expected number of people who need to receive the experimental rather than the comparator intervention for one additional person to either incur or avoid an event in each time frame. An NNT of 10 can be interpreted that one additional (or less) person will incur an event for every 10 participants receiving the experimental intervention rather than control over a given time frame. This is referred to as the NNT to benefit.

To estimate the probable clinical efficacy of a medicine for an individual, previous versions of this guidance calculated the NNT to capture the likely impact over a 12-month period.

NNT can be used as one factor in assessing the effectiveness of a particular intervention. The NNT is the average number of people who require to be treated for one to benefit compared with a control in a clinical trial. It is expressed as the reciprocal of the absolute risk reduction. For example, if the NNT to prevent one death in five years is 25 people, then the annualised NNT will be 125 (25 x 5).

Concern has been raised regarding the validity of the annualised NNT. McAlister^[48] noted that because the NNT is time-dependent, and not a linear measure over time, an extrapolation cannot be made from the NNT of a five-year trial to the lives of patients over one year in healthcare. This methodology has been used in the Scottish Polypharmacy guide since 2012. This is supported by Guthrie et al.^[49] who have proposed that the annualised NNT has value. They argue that if it is assumed that the benefits of a treatment are accrued evenly over time, and continue to accrue after the trial is finished, then the annualised NNT has validity. From a practical standpoint they argue that it offers a more simplistic measure because the prescriber is dealing with one number, rather than the NNT and duration of treatment.

Although the annualised NNT provides a numerical comparison between therapeutic interventions, this information should not be viewed in isolation as there is always a need to consider:

• What is the outcome being avoided? Death is more significant than a vertebral fracture, but different outcomes will be more or less significant to the individual.
• Over what period does the benefit accrue? Two drugs may have the same NNT to avoid one death, but the drug that achieves that over six months is more effective than that which takes 10 years.
• NNTs can be put on the same timescale by multiplying or dividing the NNT appropriately, however, this makes the untested assumption that benefit accrues consistently over time.
• The benefits of a medication should be weighed against medication related harm.
• The number needed to harm (NNH) is the average number of people taking a medication for one to suffer an adverse event. Note that risk of adverse drug reaction (ADR) is higher in older adults.

How to interpret the NNT and NNH

NNTs are only estimates of average benefit, and it is rarely possible to know precisely what the likely benefit will be in a particular patient. Prescribers and individuals should be aware of a degree of uncertainty since it is usually not possible to calculate valid confidence intervals around NNTs.

The ideal NNT is one, where everyone improves with treatment: the higher the NNT, the less effective is the treatment (in terms of the trial outcome and timescale). So if treatment with a medicine reduces the death rate over five years from 5% to 1% (very effective), the absolute risk reduction is 4% (5 minus 1), and the NNT is 100/4 = 25.

An NNT of 10 can be interpreted that one additional (or less) person will incur an event for every 10 participants receiving the experimental intervention rather than control over a given time frame.

An NNH should ideally be a high value, so large numbers of people are treated before a harm occurs.

The risk to benefit to treatment should be weighed up in each individual and may vary considerably in people with polypharmacy.

Applicability of trial data to individual adults

The drug efficacy (NNT) table provides trial population and duration information. The closer individuals are in terms of characteristics of trial participants, and duration of treatment to the trial; the more likely they will achieve the expected benefits.

Adults approaching end-of-life have an increased risk of many events, so each individual event has a higher absolute risk. This means that interventions may have a much lower NNT for that adult. This should be balanced against the shorter time they have in life to obtain a benefit, and the increased impact that any harm may have.

The NNT tables have been updated and methodology can be found in Appendix A and the table in Appendix A1.

4.8 Overview of therapeutic groups under each of the 7-Steps

Appendix B provides and overview of common medicines under therapeutic groups that might be considered under each step. In addition, Table 37 found in Appendix B sets out the BNF section.

4.9 Deprescribing as part of a person-centred approach

As a result of undertaking person-centred medication reviews using the 7-Steps process, some medicines may be identified as no longer being appropriate, and so stopped. This is often referred to as ‘deprescribing’, which is defined as the ‘planned and supervised process of dose reduction or stopping of medication that might be causing harm, or no longer be of benefit’.^[50]

A national programme found that when taking this approach, on average one to two medicines were stopped per person per review, and the rates of polypharmacy decreased.[51]^,[52] Further work in the European iSIMPATHY project, across Scotland, Northern Ireland and Ireland, found an average of 11 interventions per review from 6,481 patients. These included patient education, medicines reconciliation, medication changes and monitoring. Recommended interventions were accepted in 94% of interventions. The average number of medications reduced from 12 to 11, with 92% of the reviews resulting in more appropriate medication use, therefore decreasing the likelihood of medication-related harm. Inappropriate medications were stopped (i.e. deprescribed), reduced or altered to improve appropriateness.9

4.10 Impact of polypharmacy across care settings

There is an association between polypharmacy and death across a range of settings including the community and hospital. ^[53] Limited evidence suggests that excessive polypharmacy may have less impact on mortality risk in institutional populations compared with those living in their own home.

People living in care homes are often frail and have been identified as a priority population for medication reviews due to the increased risk of harm. The sections below set out review recommendations taking a person-centred approach. In each of the sections of the guide, evidence has been gathered using the methodology outlined in Appendix G, and considered judgement process followed to produce the strength of the recommendations. Good practice points and consensus recommendations assist by providing short statements of practical advice which may not have an evidence base but are seen as essential to good clinical practice.

4.11 Methodology used in the current guidance

As with previous versions, the literature had been reviewed to inform updates and changes. In addition, the polypharmacy group used the considered judgement process, the detail of which can be found in Appendix G. The table below summarises the relevance of the recommendations made and will support the sections that follow.

Table 2: Considered judgement options

Judgment	Recommendation	Wording for judgement
Undesirable consequences clearly outweigh desirable consequences	Strong recommendation against	Should
Undesirable consequences probably outweigh desirable consequences	Conditional recommendation against	Could
Balance between desirable and undesirable consequences is closely balanced or uncertain	Recommendation for research and possibly conditional recommendation for use restricted to trials	Consider
Desirable consequences clearly outweigh undesirable consequences	Strong recommendation for	Should
Desirable consequences probably outweigh undesirable consequences	Conditional recommendation for	Could

4.12 Medication reviews for those with polypharmacy and/or high-risk medicines across different care settings

The recommendations below are based on four systematic reviews (SRs) of acceptable quality, and realistic review. [54]^{,[55],[56],[57]} The table below sets out the recommendations on reviewing the evidence, and a considered judgment process.

Table 3: Recommendations for undertaking medication reviews for those with polypharmacy and/or high-risk medicines across different care settings

No.	Our recommendations	Strength of recommendation
1a	A structured medication review by pharmacists in primary care should be conducted at least annually.	Strong recommendation
1b	Pharmacists should consider home visits for house bound individuals to reduce the potential for hoarding of medicines by people living at home.	Strong recommendation
2	Home visits by pharmacists or GPs for house bound individuals may be effective in adjusting treatment plans and improving medication safety.	Conditional recommendation
3	Medication review should be undertaken when a person is discharged from hospital. Medication treatment in a broader sense needs to adjust and align with treatment plans; which will include medication counselling; medication self-management; and securing medication safety.	Strong recommendation
4	Medication review should follow a structured process such as the 7-Steps review process.	Strong recommendation

4.13 Prescriber interventions for the older adult with frailty receiving care at home to reduce medication related harm

Seven SRs identified prescriber interventions to reduce medication-related problems (such as falls) in people with frailty;54^{,[58],[59],[60],[61],[62],[63]} and five guidelines [64]^{,[65],[66],[67],[68]} provided recommendations for the treatment of people with frailty, which included medication interventions. These were of varying quality. A medication review (carried out by a range of different healthcare professionals) can be undertaken to identify and address medicine-related problems. See also the section on falls and medication review.

The table below sets out the recommendations on reviewing the evidence, and a considered judgment process.

Table 4: Table of medication review for people with frailty

No.	Our recommendations	Strength of recommendation
1a	Medication review to identify medication-related problems in those receiving care at home Healthcare professionals (HCP) and people over 65 years with frailty might want to discuss the importance of a medication review at least annually (regardless of the level of frailty).	Good practice point
1b	HCPs and people over 65 years with frailty might want to discuss the importance of the investigation of falls in the last 12 months.	Good practice point
2a	Person-centred medication review that recommends stopping inappropriate medication HCPs and people over 65 years with frailty might want to discuss the 7-Steps process; including reviewing the medication of all older people for the purpose of potentially discontinuing, particularly in those vulnerable to adverse effects.	Conditional recommendation
2b	Prescribers should ensure there is a valid clinical indication for current medication, and consider deprescribing corresponding medicines, where appropriate.	Good practice point
2c	Prescribers and older people with frailty should discuss reducing or stopping a medication that is no longer clinically appropriate or has more harms than benefits.	Conditional recommendation
2d	Prescribers should consider discontinuing medication when appropriate, where there is a narrow window of benefit and evidence of potential harms, especially for sedative and antipsychotic medications.	Good practice point
2e	Prescribers should follow the 7-Steps process to undertake holistic medication reviews.	Strong recommendation
3	Multidimensional interventions Medication review may identify the need for additional medications. It is important to take a person-centred approach to ensure that medicines that are needed for symptomatic control or prevention are considered where appropriate.	Good practice point

4.14 Medication review for those with polypharmacy receiving care at home and in care homes

The following recommendations were made for people receiving care at home and in care homes. People receiving care at home are potentially as frail as those living in a care home.

When considering care homes, there is the opportunity to undertake the reviews as part of an MDT.

Based on three guidelines[69]^,[70],[71] (one with mixed quality and two with lowest possible quality) and six SRs of high quality,53^{,[72],[73],[74],[75],[76]} the table below sets out the recommendations on reviewing the evidence, and a considered judgment process.

Table 5: Table of medication review for those living in a care home or receiving care at home

No.	Our recommendations	Strength of recommendation
1	Prescribers responsible for those living in care homes could utilise information from different sources, to identify those appropriate for review to reduce polypharmacy, e.g. the polypharmacy case finding indicators	Conditional recommendation
2	Relevant tools can be utilised to prioritise medication review, such as polypharmacy case finding indicators or criteria based on START/STOPP	Good practice point
3	People in care homes should have a multidisciplinary medicines review on admission and then at least yearly, in particular for potentially inappropriate medications (PIMs) and antipsychotics	Good practice point
4	Small educational group sessions can lead to a decrease in prescribing of a range of medications, including antibiotics, and neuroleptics	Strong recommendation
5	Care home staff and healthcare professionals (HCP) should be aware that certain medications can increase the risk of falls and harm caused by falls	Conditional recommendation
6	Medication Sick Day Guidance should be discussed with care staff so harm can be prevented during an episode of acute dehydrating illness.	Conditional recommendation
7	Shared decision-making (part of 7-Steps process) reflecting the stated wishes of individuals and families, to improve quality of care, is important as part of a medication review	Strong recommendation

4.15 Programmes to address polypharmacy and high-risk medication

In the iSIMPATHY (implementing Stimulating Innovation Management of Polypharmacy and Adherence Through the Years) project,9 reviews were carried out in different settings including hospital in-patient, out-patient clinics and GP practice settings. This built on the work of the EU-funded SIMPATHY (Stimulating Innovation Management of Polypharmacy and Adherence in the Elderly) project which spent two years studying polypharmacy management in Europe.2 Case studies in nine EU countries were used to determine how programs to manage polypharmacy and adherence were implemented using change-management tools such as Kotter’s eight steps and PESTEL (Political, Economic, Social, Technological, Environmental and Legal and SWOT (Strengths, Weaknesses, Opportunities and Threats).

In addition to a literature review, a benchmarking survey across the EU and a modified Delphi approach were used to establish an EU-wide consensus on how to address polypharmacy and a recommendation on what should be measured to demonstrate improvement.[77]^,[78],[79] From this, the key areas of consensus were around potential gain arising from polypharmacy management, strategic development, strategic change management, indicator measures, awareness raising and person-centred polypharmacy reviews.

In iSIMPATHY, a total of 6,481 people had a medicines review.9 The average age of those reviewed was 72 years and 53% were female. An average of six long-term conditions were recorded per person. The project pharmacists made an average of 11 interventions per review which included education, medicines reconciliation, medication changes and monitoring.

Infographic showing key findings from the iSIMPATHY evaluation:

82% of interventions were clinically significant, while 4% of interventions potentially prevented major organ failure or significant adverse drug reactions;  the appropriateness of medicines improved in 92% of reviews, with an average reduction of one medicine (from 12 to 11); economic benefits to the wider healthcare system were identified, with direct medicines cost savings of £13,100 and a potential total of £168,800 savings from avoided healthcare resource usage per 100 reviews; patients reported better understanding of their medicines, improved adherence and experienced less harm;  an average of 7.4 Quality-Adjusted Life Years (QALY) were gained per 100 patients

A number of key benefits were obtained by utilising the 7-Steps approach.

Interventions made were graded for clinical significance, with 82% being classified as clinically significant and 968 (4%) potentially preventing major organ failure, medication related harm or incidents of similar clinical importance. Recommendations were accepted in 94% of interventions. The average number of medications reduced from 12 to 11, with 91% of the reviews resulting in more appropriate medication use, therefore decreasing the likelihood of medication-related harm. Inappropriate medications were stopped (i.e. deprescribed), reduced or altered to improve appropriateness.

The changes in number of medications and improvement of appropriateness will minimise medication waste which is important to achieve both climate and sustainability strategies of the three jurisdictions. With respect to health inequalities, the criteria for review means that those from more deprived communities will benefit from reviews at younger ages due to a higher prevalence of multiple long-term conditions.

Individual experience was captured through Patient Reported Outcome Measures (PROMs). They reported large improvements in understanding, with over 90% reporting post-review that they fully understood their medicines and potential problems with them, compared with 16% pre-review. They reported reduced side effects, with 64% pre-review, reducing to 38% post-review. Improvements were also reported in people’s ability to perform their usual activities and in some parameters of medicines adherence. They also reported decreased pain, discomfort, anxiety and/or depression following these reviews.

Many people and carers were very appreciative of the opportunity to engage in reviews and very positive about the experience:

“No-one has ever sat down with me and taken time to go through all my medicines with me.”

“…huge improvement walked for half an hour this morning used to have to stop every few minutes because of the dizziness.”

The Scottish national polypharmacy programme implements the learnings from programmes such as SIMPATHY.2 Projects such as PINCER41 and DQIP42 resulted in one to two medicines reduced per person, as well as an improvement in safety and quality indicators. The priority population were those over the age of 75 years, chosen to utilise the available resources. This generated an average net saving of 150 euros per person per annum, after considering the cost of staff for the reviews.2 There were additional indirect benefits in the form of cost avoidance due to fewer adverse reactions and hospital admissions.

Another example of a program to address inappropriate polypharmacy is the study conducted in the Basque region.^[80] This study used the multidisciplinary SIMPATHY methodology to minimise inappropriate polypharmacy in a population of 360,000 citizens. This approach, with pharmacists and clinicians reviewing people with five potentially inappropriate medicines, resulted in statistically significant reductions in potentially inappropriate polypharmacy across primary and secondary care settings.

4.16 Medication appropriateness/ safety indicators

There are many measures that have been used as a measure of medication safety including the Medication Appropriateness Index (MAI),^[81] recently developed into Person-Centred Medication Appropriateness Index (PC-MAI), and medication safety indicators. These focus on assessment of the suitability of a medication for an individual considering drug interactions, drug-disease interactions and contraindications. Core indicators identified in a systemic review support these and include whether medication reviews have been conducted.[82]

Since 2018, Scotland has used a suite of 17 quality and safety indicators to monitor the appropriateness of polypharmacy. For this updated guidance, these have been peer reviewed with evidence and there are now 27 national indicators. These have been developed to include a sub analysis for care home residents. The full suite is found in Appendix C. These could be used alongside the cumulative toxicity table when multiple medications are prescribed.

4.17 Cumulative Toxicity

When many high-risk medicines are prescribed the effects of these can accumulate. Table 6 below summarises work that has been undertaken in a modified Delphi to get consensus on the harm and action to be taken. High-risk medicines combinations are also addressed in hot topics 8.41, 8.42, 8.43 and 8.44. An unabridged version of the Cumulative Toxicity Table is available as a supporting document to the consultation.

The table below summarises common adverse effects and the groups of medication which cause these. The frequency is based on the BNF definitions as follows:

• Very common: incidence equal or greater than one in 10 (≥ 1/10)
• Common: incidence equal or greater than one in 100 but less than one in 10 (≥1/100 to <1/10)
• Uncommon: incidence equal or greater than one in 1000 but less than one in 100 (≥1/1,000 to <1/100)

Note: less frequent effects are not included in the table but cannot be excluded

Table 6: Abridged Cumulative Toxicity Table

Adverse effect and frequency (where applicable)

Fall and fractures* [83]^, [84]^,[85]

Medication

ACE inhibitor/ARB

Alpha blockers for urinary symptoms

Antimuscarinics e.g. oxybutynin

Antipsychotics

Benzodiazepines and z-drugs

Beta-blocker

CCB (dihydropyridine)

CCB (verapamil/diltiazem)

Digoxin

Diuretics

Gabapentinoids

NSAIDs

Opioids

Sedative antihistamines

SSRI and SNRI

TCA

Adverse effect and frequency (where applicable)

Anticholinergic* [86]^, [87]

(see anticholinergic burden table)

Medication

Antimuscarinics, e.g. oxybutynin

Antipsychotics

Benzodiazepines and z-drugs

Digoxin

Metformin

Opioids

PPI

Prochlorperazine

Sedative antihistamines

SSRI and SNRI

TCA

Adverse effect and frequency (where applicable)

Nausea/vomiting

Very common

Medication

ACE inhibitor/ARB

Alpha blockers for urinary symptoms

Amiodarone

Antimuscarinics, e.g. oxybutynin

Antiplatelets

Antipsychotics

Benzodiazepines and z-drugs

Beta-blockers

Bisphosphonates

CCB (dihydropyridine)

CCB (verapamil/diltiazem)

Centrally acting antihypertensives

DOAC

Gabapentinoids

Gliptin

GLP-1RA

Laxatives

Metformin

NSAIDs

Opioids

Penicillins

PPI

Prochlorperazine

Sedative antihistamines

SGLT-2 inhibitor

SSRI and SNRI

Statins

Steroids

Sulfonylurea

TCA

Adverse effect and frequency (where applicable)

Dyspepsia/GI discomfort

Very common

Medication

Antimuscarinics, e.g. oxybutynin

Antiplatelets

Antipsychotics

Benzodiazepines and z-drugs

Beta-blocker

Bisphosphonates

CCB (dihydropyridine)

DOAC

Gabapentinoid

Gliptin

GLP-1RA

Metformin

NSAIDs

Opioids

PPI

SSRI and SNRI

Statin

Steroids

Adverse effect and frequency (where applicable)

Dyspepsia/GI discomfort - Common

Medication

ACE inhibitor/ARB

Adverse effect and frequency (where applicable)

Constipation

Very common

Medication

ACE inhibitor/ARB

Amiodarone

Antimuscarinics, e.g. oxybutynin

Antiplatelets

Antipsychotics

Beta-blocker

Bisphosphonates

CCB (dihydropyridine)

CCB (verapamil/diltiazem)

Centrally acting antihypertensives

Diuretics

Gabapentinoids

GLP-1RA

Metformin

Opioids

PPI

SSRI and SNRI

Statin

TCAs

Adverse effect and frequency (where applicable)

Diarrhoea

Very common

Medication

ACE inhibitor/ARB

Antimuscarinics, e.g. oxybutynin

Antiplatelets

Antipsychotics

Benzodiazepines and z-drugs

Beta-blocker

Bisphosphonates

CCB (dihydropyridine)

Digoxin

Diuretics

DOAC

Gabapentinoids

Gliptin

GLP-1RA

Laxatives

Metformin

Metoclopramide

NSAIDs

Penicillins

PPI

SSRI and SNRI

Statin

Steroids

Sulfonylurea

TCAs

Adverse effect and frequency (where applicable)

Diarrhoea - Uncommon

Medication

CCB (verapamil/diltiazem)

Adverse effect and frequency (where applicable)

Bleeding (any)

Very common

Medication

Antiplatelets

DOAC

SSRI and SNRI

Warfarin

Adverse effect and frequency (where applicable)

Bleeding (any) - Uncommon

Medication

Steroids

Adverse effect and frequency (where applicable)

Heart failure - Very Common

Medication

Beta-blocker

Adverse effect and frequency (where applicable)

Heart failure

Uncommon

Medication

Antimuscarinics, e.g. oxybutynin

NSAIDs

Steroids

TCAs

Adverse effect and frequency (where applicable)

Arrhythmias including bradycardia, tachycardia, QTc interval prolongation

Very common

Medication

ACE inhibitor/ARB

Amiodarone

Antimuscarinics, e.g. oxybutynin

Antipsychotics

Benzodiazepines and z-drugs

CCB (dihydropyridine)

CCB (verapamil/diltiazem)

Digoxin

Gabapentinoids

Opioids

SSRI and SNRI

TCAs

Adverse effect and frequency (where applicable)

Arrhythmias including bradycardia, tachycardia, QTc interval prolongation

Uncommon

Medication

Alpha blockers for urinary symptoms

Bisphosphonates

Gabapentinoids

GLP-1RA

NSAIDs

Adverse effect and frequency (where applicable)

Hypotension/dizziness

Very common

Medication

ACE inhibitor/ARB

Alpha blockers for urinary symptoms

Antimuscarinics, e.g. oxybutynin

Antiplatelets

Antipsychotics

Benzodiazepines and z-drugs

Beta-blocker

Bisphosphonates

CCB (dihydropyridine)

CCB (verapamil/diltiazem)

Centrally acting antihypertensives

DOAC

Gabapentinoids

Gliptin

GLP-1RA

NSAIDs

Opioids

PPI

Sedative antihistamines

SGLT-2 inhibitor

SSRI and SNRI

Statin

TCAs

Adverse effect and frequency (where applicable)

Hypotension/ dizziness

Uncommon

Medication

Laxatives

Sulfonylurea

Adverse effect and frequency (where applicable)

Syncope

Very common

Medication

ACE inhibitor/ARB

Antiplatelets

Antipsychotics

Beta-blocker

Adverse effect and frequency (where applicable)

Syncope

Uncommon

Medication

Alpha blockers for urinary symptoms

Bisphosphonates

CCB (dihydropyridine)

CCB (verapamil/diltiazem)

Gabapentinoids

Opioids

SGLT-2 inhibitor

SSRI and SNRI

Adverse effect and frequency (where applicable)

Respiratory symptoms

Very common

Medication

ACE inhibitor/ARB

Amiodarone

Antiplatelets

Antipsychotics

Benzodiazepines and z-drugs

Beta-blockers

Gabapentinoids

Opioids

Pioglitazone

Adverse effect and frequency (where applicable)

Respiratory symptoms

Uncommon

Medication

Bisphosphonate

CCB (dihydropyridine)

NSAIDs

SSRI and SNRI

Steroids

Adverse effect and frequency (where applicable)

Headache

Very common

Medication

ACE inhibitor/ARB

Alpha blockers for urinary symptoms

Antimuscarinics, e.g. oxybutynin

Antiplatelets

Antipsychotics

Benzodiazepines and z-drugs

Beta-blockers

Bisphosphonates

CCB (dihydropyridine)

CCB (verapamil/diltiazem)

Centrally acting antihypertensives

Diuretics

DOAC

Gabapentinoids

Gliptin

NSAIDs

Opioids

PPI

SSRI and SNRI

Steroids

TCA

Adverse effect and frequency (where applicable)

Headache

Common

Medication

GLP-1RA

Pioglitazone

Adverse effect and frequency (where applicable)

Vertigo

Very common

Medication

ACE inhibitor/ARB

Alpha blockers for urinary symptoms

Antimuscarinics, e.g. oxybutynin

Antiplatelets

Bisphosphonates

Gabapentinoids

Opioids

Adverse effect and frequency (where applicable)

Vertigo

Uncommon

Medication

Diuretics

PPI

Steroids

Adverse effect and frequency (where applicable)

Drowsiness/ Somnolence

Very common

Medication

ACE inhibitor/ARB

Antimuscarinics, e.g. oxybutynin

Antipsychotics

Benzodiazepines and z-drugs

CCB (dihydropyridine)

CCB (verapamil/diltiazem)

Diuretics

Gabapentinoids

Metoclopramide

Opioids

Sedative antihistamines

SSRI and SNRI

Adverse effect and frequency (where applicable)

Drowsiness/ Somnolence

Common

Medication

TCA

Adverse effect and frequency (where applicable)

Drowsiness/ Somnolence

Uncommon

Medication

Alpha blockers for urinary symptoms

NSAIDs

PPI

Sulfonylurea

Adverse effect and frequency (where applicable)

Confusion

Very common

Medication

Antiplatelets

Benzodiazepines and z-drugs

Beta-blockers

Gabapentinoids

Opioids

SSRI and SNRI

TCA

Adverse effect and frequency (where applicable)

Confusion - Common

Medication

Steroids

Antimuscarinics, e.g. oxybutynin

Adverse effect and frequency (where applicable)

Confusion

Uncommon

Medication

ACE inhibitor/ARB

Antipsychotics

Diuretics

Metoclopramide

PPI

Adverse effect and frequency (where applicable)

Depression

Very common

Medication Antipsychotics

Benzodiazepines and z-drugs

Beta-blockers

Centrally acting antihypertensives

Gabapentinoids

Metoclopramide

TCA

Adverse effect and frequency (where applicable)

Depression

Uncommon

Medication CCB (dihydropyridine)

CCB (verapamil/diltiazem)

Digoxin

PPI

Adverse effect and frequency (where applicable)

Visual disturbances (e.g. diplopia, blurred vision)

Very common

Medication

Antimuscarinics, e.g. oxybutynin

Antipsychotics

Benzodiazepines and z-drugs

CCB (dihydropyridine)

Digoxin

Gabapentinoids

Pioglitazone

Sedative antihistamines

SSRI and SNRI

Adverse effect and frequency (where applicable)

Visual disturbances (e.g. diplopia, blurred vision)

Uncommon

Medication

ACE inhibitor/ARB

Alpha blockers for urinary symptoms

Bisphosphonates

NSAIDs

Opioids

PPI

Statins

Steroids

Sulfonylurea

Adverse effect and frequency (where applicable)

Extrapyramidal/ movement disorders

Very common

Medication

Antipsychotics

Benzodiazepines and z-drugs

Gabapentinoids

Metoclopramide

Prochlorperazine

Adverse effect and frequency (where applicable)

Extrapyramidal/ movement disorders - Uncommon

Medication

Amiodarone

Adverse effect and frequency (where applicable)

Hypoglycaemia

Very common

Medication

GLP-1RA

SGLT-2 inhibitor

Adverse effect and frequency (where applicable)

Hypoglycaemia

Common

Medication

Gliptin

Sulfonylurea

Adverse effect and frequency (where applicable)

Hypoglycaemia

Uncommon

Medication

ACE inhibitor/ARB

Gabapentinoids

Statins

Adverse effect and frequency (where applicable)

Electrolyte disturbance e.g. hypokalaemia, hyperkalaemia, hyponatraemia

Very common

Medication

ACE inhibitor/ARB

Antiplatelets

Bisphosphonates

Diuretics

Steroids

Adverse effect and frequency (where applicable)

Electrolyte disturbance e.g. hypokalaemia, hyperkalaemia, hyponatraemia

Uncommon

Medication

Antipsychotics

Laxatives

NSAIDs

SGLT-2 inhibitor

Adverse effect and frequency (where applicable)

Renal injury

Very common

Medication

ACE inhibitor/ARB

Bisphosphonates

Adverse effect and frequency (where applicable)

Renal injury

Uncommon

Medication

GLP-1RA

SGLT-2 inhibitor

Adverse effect and frequency (where applicable)

Urinary retention

Very common

Medication

Antimuscarinics, e.g. oxybutynin

Antipsychotics

NSAIDs

Opioids

Adverse effect and frequency (where applicable)

Urinary retention - Common

Medication

TCA

Adverse effect and frequency (where applicable)

Urinary retention

Uncommon

Medication

CCB (dihydropyridine)

Gabapentinoids

SSRI and SNRI

Adverse effect and frequency (where applicable)

Blood disorders including agranulosis, neutropenia, anaemia, thrombocytopenia

Very common

Medication

Amiodarone

Antipsychotics

DOAC

Gabapentinoids

Penicillins

Prochlorperazine

Statins

Adverse effect and frequency (where applicable)

Blood disorders including agranulosis, neutropenia, anaemia, thrombocytopenia

Uncommon

Medication

ACE inhibitor/ARB

Diuretics

NSAIDs

PPI

Steroids

Adverse effect and frequency (where applicable)

Rash, pruritis, skin reactions

Very common

Medication

ACE inhibitor/ARB

Amiodarone

Antimuscarinics, e.g. oxybutynin

Antiplatelets

Antipsychotics

Beta-blockers

Bisphosphonates

CCB (dihydropyridine)

CCB (verapamil/diltiazem)

Digoxin

Diuretics

Gabapentinoids

Gliptin

GLP-1RA

NSAIDs

Penicillins

PPI

Prochlorperazine

SGLT-2 inhibitor

SSRI and SNRI

Steroids

TCA

Adverse effect and frequency (where applicable)

Rash, pruritis, skin reactions

Uncommon

Medication

Alpha blockers for urinary symptoms

Benzodiazepines and z-drugs

Centrally acting antihypertensives

DOAC

Statins

Adverse effect and frequency (where applicable)

Muscle pain/weakness

Very common

Medication

ACE inhibitor/ARB

Bisphosphonates

Diuretics

Gabapentinoids

SSRI and SNRI

Statins

Adverse effect and frequency (where applicable)

Muscle pain/weakness

Uncommon

Medication

Antipsychotics

Beta-blockers

CCB (dihydropyridine)

CCB (verapamil/diltiazem)

NSAIDs

PPI

*Falls and fractures and anticholinergic effect: it is not possible to determine the frequency of these as the adverse effect is caused by multiple factors

Abbreviations: ACE inhibitor: angiotensin-converting enzyme inhibitor, ARB: angiotensin II receptor blocker, CCB: calcium channel blocker, DOAC: direct-acting oral anticoagulants, GLP-1RA: glucagon-like peptide-1 receptor agonists, NSAID: non-steroidal anti-inflammatory drugs, PPI: proton pump inhibitors, SGLT-2 inhibitor: sodium-glucose co-transporter 2 inhibitors, TCA: tricyclic antidepressant

4.18 Case Finding Indicators

To identify those at most risk of harm, the medication case finding indicators have been used to prioritise these patients for review. An evidence review has been undertaken of the indicators. These have then gone through a research and development process to reach consensus on the inclusion of the indicators, taking into consideration the prevalence of the safety issues. There are 69 case finding indicators. These are detailed in Appendix D These have been developed into a computerised decision-making tool in the GP IT system and is approved by the Medicines and Healthcare Regulatory Agency (MHRA).

4.19 Templates for recording review and coding for review

A polypharmacy review is a medication review following the principles of the 7-Steps, that considers all the clinical information and where outcomes from the review are discussed with the individual and/or carer; either face to face or remotely.

An electronic template is available for both Vision and EMIS that can be used in the consulting system and will automatically read code the reviews and the interventions made. This can be found in Appendix O with a link to instructions on how to implement this.

When reviews are undertaken without the above template, to facilitate evaluation on the impact of polypharmacy reviews and outcomes, the reviews should be digitally recorded, adding read code 8B31B for primary care records. The key information summary (KIS) should also be updated. This will ensure that as individuals move across transitions of care, there is continuity in the management of their medicines.

4.20 Economic impact of undertaking reviews

A systematic review found that interventions to optimise medication use have benefits that outweigh the costs. A narrative review on the impact of interventions to decrease polypharmacy found that economic benefits are important factors to consider.^[88] However, the scale up of such studies in this area are limited and need to address the barriers and enablers. The SIMPATHY project set out the key elements to scale up a program to address inappropriate polypharmacy and developed the economic modelling from the 2015 Polypharmacy guidance. The iSIMPATHY program has scaled these findings in three EU countries. A summary of the findings are given below and the detailed analysis can be found in the full evaluation report on the iSIMPATHY website.

The analysis determined that, on average, per 100 reviews:

• cost £7,500 (€8,786) to deliver
• results in £13,100 (€15,346) direct savings associated with medication changes

Healthcare cost avoidance and patient benefits per 100 reviews:

• theoretical projection of potential avoided admissions could be associated with £6,600 (€7,731) indirect savings from avoided adverse drug reaction-related hospital admissions (in-patient costs)
• linking recorded Eadon scores to cost avoidance and quality adjusted life year (QALY) gains estimated an average of £168,800 (€197,800) in medical costs and a 7.4 QALY gain, using Eadon intervention classification calculations

The total cost reduction from net medication changes alone would more than outweigh the staff cost for the Republic of Ireland and Scotland. With either the bottom-up or top-down approaches to economic analysis, the benefits (cost avoidance) would outweigh the associated direct cost in all three regions.

If comprehensive medicine reviews were provided to all patients aged over 65 years (over 75 years in Northern Ireland), taking five or more medicines in each country the maximum avoidable inpatient cost would be £24.7 million (€28.9 million) for Ireland; £11.0 million (€12.9 million) for Northern Ireland; and £36.0 million (€42.1 million) for Scotland.

The iSIMPATHY model has been demonstrated to be generally applicable in a range of healthcare settings and in different healthcare systems. There has been interest both at European level and globally to adopt this methodology to address this public health challenge.[89]^,[90]

4.21 Addressing Health Inequalities

Individuals at highest risk of inappropriate polypharmacy are those with the greatest frailty, and on the most medicines and taking high risk medicines. Analysis from Scottish data shows that those in the most deprived communities take the greatest number of medicines, and analysis of high-risk combinations show that these are highest in the most deprived areas. We also know that life expectancy is lower, and disease burden higher in areas of deprivation.

While the main drivers of health inequalities lie outwith health services, our services and the way we deliver them play an important role. In this small section we raise awareness of health and healthcare inequalities and connect to emerging evidence on effective ways of mitigating inequalities in healthcare. This section is supported by Appendix J where fuller explanations and literature citations are given, including the intersectional nature of health inequalities i.e. that health inequalities can be more fully understood by exploring factors beyond only socioeconomic deprivation.

Scotland has high levels of health inequalities, ^[91] with poorer areas recently experiencing worsening health. Health inequalities are ‘unjust and avoidable differences in people’s health across the population and between specific population groups’, [92] meaning that when it comes to differences, we should consider what differences are avoidable and what are not. Polypharmacy is a good example; Chart 1 below shows increasing medicines with age, elements of this are not avoidable, however, the chart also shows large differences between areas of relative affluence and deprivation – factors here are avoidable (and also complex).

Data confirms that there is greater prescribing in higher SIMD categories, indicating polypharmacy and multimorbidity (see Chart 1)

Actions on health inequalities

In the context of undertaking medication reviews, approaches to care can be adopted to account for some of the factors that maintain inequalities. If any service improvement approaches are being undertaken, accounting for equitable care should be considered, and Appendix J contains further details of supporting literature and resources to help.

Approaches to consider in delivering care include:

• Raising healthcare professional (HCP) education and awareness of health inequalities, driving factors, impacts on individuals and the limitations of tackling inequalities solely through healthcare
• Consideration of additional support that might be needed to reduce barriers at service interfaces e.g. support mechanisms to help attendance at specialist appointments or care coordinators
• Continuity, building relationships and trust in delivery of care is helpful in particular for marginalised groups. Service design aspects to consider: continuity in timetabling, personal lists and longer consultations
• Improving healthcare professionals’ understanding of power imbalance – understanding that different groups may hold different levels of power that influences consultations, and can inhibit people asking questions that matter, leading to over-medicalisation
• Health literacy involves a functional understanding of any health condition. It supports the ability and opportunity to implement management and to navigate health systems. To promote health literacy within healthcare, use verbal communication strategies, accessible information, easy-to-navigate services and flexible care
• Trauma-informed approaches to health service provision are typically service-wide with connections to trauma treatment options. In consultations it is important to give space to develop trust and for people to tell their stories; fostering individual choice and control, and being sensitive and aware of cultural, historical and gender-related issues
• Welfare and financial inclusion – HCPs can routinely enquire about money worries and signpost patients to welfare resources e.g. Citizen’s Advice Bureau

4.22 Who should be targeted for review?

There has been a comprehensive review of the case finding criteria which identifies individuals who may benefit the most from a polypharmacy review. In the previous version of this guidance, these criteria were based on age, residency in a care home, number of repeat medicines prescribed and Scottish Patients at Risk of Readmission and Admission (SPARRA) score of 40-60%. This guidance recommends the use of the Rockwood Clinical Frailty Scale ^[93] and the eFrailty Index [94] to determine frailty and prioritise these individuals for review.

Trial evidence demonstrates the importance and impact of targeting those with high-risk prescribing.29^,35^,36^,37^,39^,41^,42^,[95], Holistic face-to-face reviews reduced the risk for these individuals and demonstrated a reduction in hospital admissions for acute kidney injury. The success of this approach has been used by the Data and Indicator sub-group and the guidance development group to consider a wider range of Case Finding indicators to target those on high-risk medications (Appendix D1). These indicators have undergone peer review.

Another important area that the guidance development group considered was the effect of deprivation on rates of polypharmacy. The review of polypharmacy prescribing data (10 or more medicines including a high-risk medicine) by deprivation demonstrates that multimorbidity, and its associated problems, presents 10 to 15 years earlier in more deprived communities.

The following revised case finding criteria are recommended to prioritise individuals for a polypharmacy medication review:

A. Prescribed 10 or more medicines with a high-risk medication (this will identify those from deprived communities where the average age is lower when taking 10 or more medications)

B. Adults aged 50 years and older and resident in a care home, regardless of the number of medicines prescribed

C. Adults aged over 65 years, prioritising those living with frailty or anyone over 75 years

D. Adults of any age, approaching the end of their life or receiving palliative care

E. Those receiving care at home or hospital at home

F. Those on high-risk medication (as defined by the Case Finding indicators (Appendix D1), regardless of the number of medicines taken

4.23 Who is this guidance targeted at?

Everyone, including patients, policy makers and healthcare professionals, has a role to play in ensuring that when people are taking multiple medicines that they only take the medication they require, and it is safe and appropriate.

Recommendations have been based on the best evidence available. More research is needed and there are large gaps in knowledge. The guidance therefore has used expert opinion and contains a large range of realistic case studies that aim to give pragmatic advice on how to manage the many difficult situations where evidence is lacking. It will take all members of the healthcare team to bring about significant improvement in this area, and utilising the multidisciplinary team for more complex interventions should be considered.

The core principle of Polypharmacy Guidance: Appropriate Prescribing - Making medicines safe, effective, and sustainable 2025-2028 is the holistic person-centred 7-Steps medication review. The principles should be considered at all critical stages of the medication use process: prescribing; reviewing; dispensing; communicating and reconciling. This is of particular importance at initiation of treatment to support shared decision-making between the individual (and/or carers, and/or welfare proxies) and the healthcare professional.

Individuals play a vital role, if provided with the right information, tools and resources to make informed decisions about their medicines. Although many of the resources provided are aimed at healthcare professionals, the ManageMeds app, patient leaflets and revised Medication Sick Day Guidance and Patient Reported Outcomes Measures (PROMs) are available to aid individual understanding and involvement, through shared decision-making.

4.24 Emerging areas of research and development (Pharmacogenomics, AI)

Pharmacogenomic testing has the potential to improve medicines optimisation by providing information on the individual’s response to treatment, taking a person-centred approach. This will result in less medication related harm and improved outcomes. Some studies have shown that this approach is more economically viable.

There is an increasing interest in the role of AI to identify individuals at most risk of harm from multiple medicines and use of AI in the decision-making on the actions to take from a medication review. Summaries of the literature reviews can be found in Appendix K and Appendix L.

However, more evidence is needed together with a tested framework for implementation. A recent overview^[96] of the current status and future perspectives of pharmacogenomics discusses current practice, the potential to use genomic technologies to maximise efficacy and minimise toxicity of medications. A number of research priorities are highlighted and include the evaluation of the role of pharmacogenomics in older adults living with multiple long-term conditions for both medicine optimisation and deprescribing. Scottish Government will be building on the iSIMPATHY project with the Innovation in person-centred Medication Prescribing and Review for Optimal Value and Efficacy (iMPROVE) project, starting in March 2025 to determine the value of pharmacogenomic in medication reviews using the 7-Steps process.